This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. After completing the informed consent process, potential volunteers will complete outpatient screening, including assessment of inclusion/exclusion criteria. This will be a double-blind, placebo-controlled, within-subjects study. The study will be conducted in 20 non-treatment seeking cocaine (COC)-dependent subjects who will reside in the Michael De Bakey VA Medical Center during two separate 5-day visits. After admission and stabilization (day 1), participants will be randomly assigned to placebo or disulfiram (250mg qd). Participants will take the study drug on days 2-4. On day 4, participants will participate in two COC self-administration in which they will have the opportunity to choose between COC (0 and 20 mg, IV) or money alternatives. On day 5, participants will be discharged from the study and will return a minimum of 7 days for enrollment and randomization to alternate disulfiram dosing conditions. During the 2nd inpatient phase, participants will receive payment for prior enrollment and staff will assess late emerging adverse events. Participants will receive payments of $50 per day provided they abstain from illicit cocaine use. We anticipate that disulfiram treatment will be associated with reduced cocaine self-administration. Results of the proposed research will provide information about the predictive value of two different laboratory models of cocaine self-administration. If results from either or both of these laboratory models are congruent with outcomes from published clinical trials of disulfiram, then further research aimed at optimizing design parameters would be indicated to further develop these approaches. The development of valid laboratory models would greatly facilitate the search for more effective treatments for cocaine dependence. To determine the effects of treatment with disulfiram on cocaine self-administration using a human laboratory model of cocaine self-administration.